The dura mater is a functionally significant structure in the anatomy of the central nervous system, forming a membrane system which envelops the entire central nervous system and protects it from external influences.
The dura mater may require repair due to a number of causes, including trauma, inflammatory or neoplastic processes, surgical procedures, or congenital abnormalities. The need to close dural defects, especially following surgical procedures and in the presence of posttraumatic fistulae, has prompted a quest for the ideal dura mater substitute. These defects may result in postoperative complications, in particular, seepage of cerebrospinal fluid, infections, and resultant cerebral seizures. Some form of dural graft procedure is required in association with almost 30% of craniotomies. As the primary closure of the dural defect often fails, the availability of a dural substitute to avoid the above complications is of great practical significance.
A permanent liquid-tight closure of the dura mater is required to avoid cerebrospinal fluid leakage after skull injuries or surgical interventions to remove malignant tumors in the brain or spinal column. Neurosurgeons currently use resorbable or non-resorbable dura mater substitutes and usually attach them to the dura mater in the cranium or spinal column with sutures and/or fibrin glue. Examples of resorbable materials have included human cadaveric dura mater, human fascia lata, bovine pericardium, xenogen collagen-sponges, and implants from woven materials, consisting of resorbable polyester (polyglactin and/or poly-p-di-oxanon). Examples of non-resorbable dura substitutes include materials made of poly-tetra-fluoro-ethylene (PTFE) or polyester urethane.
Almost all dural grafts studied to date are associated with complications, some major. The main complications that have been reported are chronic inflammatory and rejection reactions and the formation of corticomeningeal adhesions resulting among other things in the development of epileptogenic foci. Haematomas and cerebrospinal fluid fistulae are also observed, which in turn provide a point of entry for various-disease-causing organisms.
Numerous materials and methods have been evaluated over the past decades in quest of the ideal dural graft, including various metallics, implants, synthetic materials, autologous tissue transplants and preserved human cadaveric dura mater. Most of these products are unsuitable because of the associated postoperative complications, some of them serious. Examples of the complications include chronic inflammatory and rejection reactions, development of corticomeningeal adhesions, haemorrhages, and encapsulation of dura mater grafts in a thick layer of connective tissue. Previous studies on the subject of suitable dural replacements show that early graft absorption coupled with formation of an endogenous neodura are the main factors predictive of uneventful and permanent dural fusion.
Several autologous tissues have been used in the past as dura mater substitutes. In 1911, Kostling used a patient's hernial sac to form a dural graft. Kostling, W., Med Wochenschr, 58, 1042 (1911). Other autologous tissues such as temporal fascia, fascia lata femoris and periosteal flaps have been used since then. Barrow et al. successfully reconstructed a large dural lesion with endogenous greater omentum. Barrow et al., J. Neurosurg. 60; 305-1 (1987). The advantage of autologous grafts is that there is no risk of pathogen transmission or tissue rejection. However, the additional removal of tissue increases the surgical trauma and prolongs what is probably in any case a complicated surgical procedure.
Preserved human cadaveric dura has been used routinely for many years as a dura mater substitute for dural replacement in human subjects. These preparations consist of connective tissue fibres which are interwoven like the body's own dura mater. After the cadaveric human dura mater are utilized in neurosurgery, they are said to form a liquid-tight closure, similar to the body's own dura mater, and are eventually replaced by the body's own tissue during a degradation process over an extended period of time. The cadaveric-derived material is preserved by freeze-drying (lyophilization) and gamma sterilization (Lyodura, B. Braun Melsungen Aktiengesellschaft, Melsungen, Germany) or in a multistage chemical process (Tutoplast® process; Tutoplast® Dura, Tutogen Medical GmbH, Neunkirchen am Brand, Germany). Human cadaveric dura mater grafts, however, have been associated with significant risks in carrying viruses and prions, which can cause the feared disease spongiform encephalitis (Creutzfeldt-Jakob disease or Gerstmann Streussler syndrome). Due to numerous deaths occurring after implantation of human dura mater, the use of human cadaveric dura mater grafts has been restricted or banned in a number of countries.
Human fascia lata and pericardium preparations have also been used as dura mater substitute material with less danger of transmitting infectious agents than human cadaveric dura mater. While these preparations carry less risk of transmitting disease, they are resorbed slowly over periods of months or years which can result in scar formation and encapsulation of the dura substitute material.
Dura substitutes have also been derived from non-human sources such as bovine or porcine collagen isolated from skin or tendons and bovine pericardium tissue. Similar to human-derived sources, some bovine dura substitutes have been believed to transmit disease, namely bovine spongiform encephalopathy (BSE), to the patient receiving the dura mater graft. Use of porcine derived dural substitutes, however, resulted in adhesions with the underlying cerebral tissue.
Narotam et al., U.S. Pat. No. 5,997,895, disclose dural substitutes derived from treated xenogenic collagen in the forms of porous collagen sponge, felt, or film. The treatment of collagen inactivates viral and prion contamination such that the substitute does not contain infectious amounts of viruses and prions. Porosity of dura substitutes is disclosed as necessary to permit vessels, cells and meningeal tissue to infiltrate the dura substitute. In clinical practice, however, the application of the available porous materials is connected with disadvantages, since shape stability and primarily liquid tightness are not always guaranteed. Narotam et al. also disclose a dura substitute which is a sandwich of two or more forms of collagen sponge, felt, or film wherein at least one form is sufficiently porous for ingrowth of meningeal tissue.
Resorbable polyesters are also available for clinical use but have the disadvantage of low elasticity and slow degradation. In special situations these implants cause wound healing problems and may increase infection.
Foils or sheets consisting of a metal such as gold, platinum, silver, nickel, tantalum, or steel, or polymers such as polytetrafluoroethylene (PTFE) or other polyesters, have also been used as dura mater substitutes. These substitutes are not absorbed by the patient, however, but become encapsulated in a tough layer of connective tissue and remain in the body for the life of the patient as a foreign body without substitution by the body's own structures. This can result in a high risk of germ growth in the inner pores which cannot be controlled by the body's own defence mechanism, due to the porous structure of the PTFE foil membranes.
Collagen-based products are becoming increasingly popular. Chemical processes can be used to modify structures with a high connective tissue component, such as the pericardium or dermis, so that only an acellular, antigen-free collagen scaffold is preserved. Products are available which consist entirely of collagen fibrils or collagen-coated synthetic materials. In both cases the collagen fibre network acts as a matrix for growing endogenous connective tissue.
Chaplin et al. tested a product obtained from guinea pig skin (XenoDerm, Lifecell Corp., The Woodlands, Tex.) in an animal model. Neurosurgery, 45:2, 320-7 (August 1999). The comparator was autologous pericranium. The epidermis, all cellular components, and other potentially antigenic or infectious elements were chemically removed in the manufacturing process. The collagen fibres and structural architecture of the skin were preserved unchanged. The product was rapidly reported to incorporate with the surrounding dura in the presence of a mild cellular response. Invading fibroblasts were observed preferentially at the implantation site. The graft and original dura mater were said to be barely distinguishable at the end of the study 6 months postoperatively.
Following on from these results, Warren et al. (2000) investigated AlloDerm® (LifeCell Corp., The Woodlands, Tex.) for dural replacement in human subjects. Neurosurgery 46(6):1391-96 (2000). Two hundred patients received an AlloDerm dural graft during the study. This material is obtained from human dermis. The manufacturing process is said to be the same as for XenoDerm, producing an acellular collagen biomatrix that is major histocompatibility complex (MHC) antigen free. Seven of the 200 patients developed postoperative complications such as infection and cerebrospinal fluid (CSF) fistulae, but none of these incidents was reported as caused by the graft itself. Surgical revision was said to show that none of these patients had developed adhesions or rejection reactions at the dural graft site. The material was said to be highly similar to the surrounding dura on macroscopic examination. Long term study data on this product are not yet available.
Filippi et al. (2001) described experiments in the use of solvent preserved gamma sterilized bovine pericardium (Tutopatch®, Tutogen Medical GmbH, Neunkirchen, Germany) for dural replacement in 32 subjects. Filippi, et al., Neurosurg. Rev., 24:103-107 (2001). The postoperative course was said to be uneventful in all but one patient, who died of cardiac causes shortly after the operation. The graft was described as easy to handle, durable and low-cost. Long term study data ruling out possible late complications are not yet available.
Collagen products are suitable for use as biomaterial on many accounts: the chemotactic interaction in which they engage facilitates rapid infiltration of endothelial cells and fibroblasts, which in turn produce and deposit new collagen fibres; a concomitant limited lymphocytic inflammatory response in surrounding structures promotes absorption of the collagen biomatrix. Collagen also possesses haemostatic properties which are put to therapeutic use. Platelets deposit themselves on the collagen structure, disintegrate and in doing so release clotting factors which facilitate fibrin formation in conjunction with plasma factors.
Known dura substitute materials and related methods of using such materials fail to provide a liquid-tight, resorbable substitute dura mater that avoids encapsulation, dura scar formation, or adhesion to cerebral tissue, and furthermore has a low risk of transmitting germs, viruses, and prions which can cause spongiform encephalitis or other diseases. An ideal dura mater replacement should not engender an immune defence response or inflammation and must be non-toxic. It should be rapidly absorbed and at the same time allow connective tissue architecture to build up so that an endogenous neodura develops. The graft should not adhere or fuse with cerebral tissue or bone during this process. The material should be resistant to tearing, keep its shape, and resist cerebrospinal fluid permeation. The replacement dura mater also should be stable in its volume and shape wherein it resists expansion or contraction after implantation. Other important criteria are viral and prion safety, user friendliness and economical manufacturing cost.